The recent introduction of the DSM-III classification of Anxiety Disorders represents a distinct advance for empirically based diagnostic practice. Yet, the field of anxiety has lagged behind other areas of psychiatric research, so that little is known about the diagnostic validity, biochemical markers and underpinnings, pathophysiological mechanisms, patterns of transmission or effective treatments for the various anxiety disorders. This program-project represents a broad based based attempt to fill in a number of these gaps in knowledge by applying to the field of anxiety those techniques that have produced major advances in our understanding and ability to treat the affective and schizophrenic disorders. We plan a broad range of interrelated psychobiological, family and treatment studies of Agoraphobia with Panic Attacks, Panic Disorders, Generalized Anxiety Disorder, Obsessive-Compulsive Disorder and Simple Phobias. To accomplish this, a broad collaboration by a variety of distinguished investigators has been established. The psychobiological investigation involve an expansion of our studies of lactate induced provocation and pharmacological blockade of panic attacks. Prior studies in this area have already lead to major revisions in psychiatric diagnosis and treatment of anxiety disorders. We propose to conduct standard and modified lactate studies in patients with a variety of DSM III Anxiety Disorders. We will also conduct hyperventilation, Holter monitoring, echocaridiogram and biochemical-physiological assessment. Coupled with this will be diagnostic-specific treatment studies to resolve pressing, unanswered questions. Specifically proposed are in vivo exposure vs. Imipramine in Agoraphobics, benzodiazepine vs. relaxation for GAD patients, desmethylimipramine vs. clomipramine for Obsessive-Compulsives, and a variety of specific and practical pharmacological trials with panic patients. Family studies to assess type and prevalence of psychiatric disorders in first degree relatives of study probands are also planned. Our goal is to assess the relative degree of homogeneity or heterogeneity of DSM-III Anxiety Disorders using psychobiological, family illness, and treatment response data as validating criteria.